Increased number of microglia and enhanced expression of inflammatory factors in the hippocampus of rat model of depression

Abstract

Objective To investigate the changes of the total microglial number, density of activated microglia and inflammatory cytokines in the hippocampus of rat model of depression induced by chronic unpredictable stress (CUS). Methods Male Sprague-Dawley (SD) rats (6~8 weeks old) were randomly divided into control group (n=19) and CUS intervention group (n=48) with stratified randomization after adaptive feeding, sucrose preference baseline adjustment and screening. The rats of CUS intervention group were subjected to CUS intervention for 5 weeks. The depressive-like symptoms of 2 groups of rats were assessed with the sucrose preference test, and 16 model rats were screened out according to the results of sucrose preference. Immunohistochemical assay and stereological method were used to quantify the total number of microglia in the hippocampus of 2 groups of rats. The density of activated microglia in the hippocampus were studied with immunofluorescence assay. The contents of inflammatory cytokines in the hippocampus were measured with quantitative real-time polymerase chain reaction (qRT-PCR). Results The body mass and percentage of sucrose preference were significantly lower in the CUS model group than in the control group (P < 0.01). The numbers of the microglia in the hippocampal CA1, CA2/3 and DG regions were significantly increased in the CUS model group compared with the control group (P < 0.001, P=0.002, P=0.002), so were the density and proportion of the activated microglia in the CA1, CA2/3 and DG regions (P=0.011, P=0.015, P < 0.001; P=0.018, P=0.019, P < 0.001). Compared with the control group, the mRNA levels of inflammatory cytokines IL-1β and iNOS in the hippocampus were obviously higher in the model group (P=0.012, P=0.020). Conclusion The number of the microglia, density and proportion of activated microglia as well as levels of inflammatory cytokines are increased in the hippocampus of depression rats, indicating that the changes of hippocampal microglia might be involved in the pathogenesis of depression.

Keywords

• depression
• hippocampus
• microglia
• interleukin-1beta
• inducible nitric oxide synthase
• stereology